Amino sugars are usually found as monomer residues in complex oligosaccharides and polysaccharides. Glucosamine is an amino derivative of the simple sugar, glucose. N-acetylglucosamine is an acetylated derivative of glucosamine. Glucosamine, N-acetylglucosamine and other amino sugars are important constituents of many natural polysaccharides. For example, polysaccharides containing amino sugars can form structural materials for cells, analogous to structural proteins.
Glucosamine is manufactured as a nutraceutical product with applications in the treatment of osteoarthritic conditions in animals and humans, among other conditions. The market for glucosamine is experiencing tremendous growth. Furthermore, significant erosion of the world market price for glucosamine is not expected. N-acetylglucosamine is also a valuable pharmacological agent in the treatment of a wide variety of ailments. N-acetylglucosamine does not have any established negative side effects. Since N-acetylglucosamine is a valuable and important component of protein synthesis in the animal body it has a positive effect on tissue regeneration, N-acetylglucosamine has therapeutic potential in the prevention and/or treatment of a wide variety of diseases such as gastritis, food allergies, inflammatory bowel disease (IBD), diverticulitis, acute and chronic forms of rheumatoid arthritis and osteoarthritis, as well as the pathological conditions arising from metabolic disorders of the osteoarticular tissues.
Glucosamine is currently obtained by acid hydrolysis of chitin, a complex carbohydrate derived from N-acetyl-D-glucosamine. Alternatively, glucosamine can also be produced by acid hydrolysis of variously acetylated chitosans. Chitin, a copolymer of N-acetylglucosamine and glucosamine, is a common natural substance, found in arthropods and fungi. It can be obtained from inexpensive sources like arthropod refuse, e.g.: shellfish (lobster, shrimp, krill, crab, and prawn exoskeletons); insects used to biodegrade swine offal like the fly larvae; and more recently from waste fungal biomass used in citric acid production. The final product, salts of glucosamine, are relatively expensive because the relatively low chitin content in refuse sources requires large volumes of waste to be processed in order to obtain relatively small amounts of product, and because the processing itself is relatively low yield and energy and chemically intensive.
Common industrial practice is to purify the chitin by treating it with combinations of acids and bases to remove minerals, proteins and other impurities accompanying the offal starting material, and to then depolymerize and deacetylate the chitin in a single step to glucosamine through the use of concentrated hydrochloric acid at high temperature, long times and low yields. Glucosamine as a free base is very unstable and subject to degradation. Consequently stable salts such as the hydrochloride are produced. Other blends of salts are offered, usually using the hydrochloride as a base, in order to mimic forms that have been tested for efficacy in clinical settings like Viartril and DONA® 200-S. These compositions take the form of mixed salts with a molecular formula of (glucosamine)2 sulfate-(NaCl)2, and (glucosamine)2 sulfate-(KCl)2. More recently, salts of the structure (glucosamine)2 sodium bisulfate-(HCl)2, (glucosamine)2potassium bisulfate-(HCl)2 are being investigated as means to provide stable salts of glucosamine, at lower sodium and potassium dosages.
N-acetylglucosamine is not widely available in the marketplace. It is currently produced by the acetylation of glucosamine using an organic acetylating reagent such as acetic anhydride, an expensive and difficult step. These processes suffer from poor product yields (in the range of 50% conversion of substrate to glucosamine).
The common forms of glucosamine, being derived from shellfish, carry labels warning consumers of the potential for allergic reactions in persons sensitive to shellfish. Increasingly, consumers are seeking access to material that is free of all animal byproducts. Moreover, the availability of raw material (i.e., a source of chitin, such as crab shells) is becoming increasingly limited. Therefore, there is a need in the industry for a cost-effective method for producing high yields of glucosamine and N-acetylglucosamine for commercial sale and use.
PCT Publication No. WO 02/66667 disclosed glucosamine and method of making glucosamine from microbial biomass. This method of production overcomes problems associated with shellfish allergy, but it suffers from a major problem of low yield. More particularly, since the method relies on the biomass waste generated in a fermentation that is dedicated to the production of other products such as citric acid, it is not sufficient to produce quantities of glucosamine that meet the increasing market demand for the product. U.S. Pat. No. 6,372,457, incorporated herein by reference in its entirety, disclosed a process and materials for production of glucosamine by microbial fermentation. However, U.S. Pat. No. 6,372,457 does not disclose any method for the production of N-acetylglucosamine.